Effects of transcutaneous auricular vagus nerve stimulation on perioperative anxiety in patients undergoing laparoscopic colorectal cancer surgery: a study protocol for a double-blind, prospective, single-centre, randomised controlled trial.

Introduction
Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related mortality worldwide. Surgical treatment is currently the preferred therapeutic option for patients with CRC.1 With the improvement of early detection and surgical outcomes, attention in clinical practice is now focused not only on disease progression but also increasingly on the quality of life and mental health of patients after treatment. Perioperative anxiety refers to the fear, nervousness and worry that patients experience toward unknown factors related to their disease, anaesthesia and surgery during the perioperative period.2 3 50%–70% of patients were reported to experience anxiety during the perioperative period,46 accompanied by symptoms such as fatigue, difficulty concentrating and muscle tension.7 8 Perioperative anxiety could potentially bring about some side effects, such as elevated concentrations of cortisol, angiotensin and catecholamines in the blood, causing haemodynamic abnormalities.9 10 In addition, perioperative anxiety can exacerbate pain, delay wound healing, increase the risk of infection and cause a decline in postoperative cognitive function, among other issues.11 Older patients are identified as a high-risk group for perioperative anxiety owing to factors such as advanced age, a higher prevalence of comorbidities, pronounced loneliness and relatively weak social support.12 With the advancement of surgical procedures and increasing number of older patients, the incidence of perioperative anxiety is anticipated to escalate, thereby emerging as a pivotal factor influencing patient prognosis. Therefore, implementing effective anti-anxiety measures is highly necessary.
Currently, various measures have been implemented to address perioperative anxiety. The main measures include preoperative assessment and education, pharmacological treatment and non-pharmacological interventions. Pharmacological treatment primarily involves the preoperative administration of benzodiazepines, such as midazolam and dexmedetomidine.13 14 However, these methods often come with certain limitations and are accompanied by a multitude of unfavourable responses, such as respiratory depression, drowsiness, nausea, vomiting and hyperalgesia.1519 These side effects will adversely affect the patient prognosis and recovery and prolong the hospital stay. Non-pharmacological approaches, including patient education and music therapy, are increasingly drawing significant public interest and recognition.20 When combined with appropriate pharmacological treatments, they can effectively reduce the occurrence of perioperative anxiety in patients. In this context, transcutaneous auricular vagus nerve (VN) stimulation (TaVNS) has emerged as a promising non-invasive neuromodulation technique.21 By delivering a weak electrical current through electrodes to stimulate the auricular branch of the VN (ABVN), TaVNS could regulate the nervous system and influence the projection of brain nuclei.
The ABVN primarily innervates the external auditory meatus and concha region. It belongs to the general somatic sensory afferent mixed branch, projecting not only to the spinal nucleus of the trigeminal nerve but also maintaining close fibre connections with the solitary nucleus. TaVNS stimulates the ABVN on the skin surface, which then enters the VN trunk and projects to the solitary nucleus. This activation subsequently stimulates the ventral medulla and dorsal motor nucleus, thereby regulating central autonomic nervous activity.22 Clinical studies suggest that TaVNS improves emotional regulation by modulating limbic–cortical circuits, such as enhancing connectivity between the anterior cingulate cortex and amygdala. TaVNS effectively reduces the seizure frequency in patients with refractory epilepsy and improves the Hamilton depression rating scale (HAM-D) scores of patients with depression.23 TaVNS also improves anxiety and sleep quality in patients with chronic insomnia. Preclinically, TaVNS promotes neuroplasticity and enhances GABAergic inhibition, potential mechanisms underlying its anxiolytic effects. TaVNS may exert anti-anxiety and depressant effects through potential mechanisms such as promoting neural plasticity, increasing the secretion of gamma-aminobutyric acid and inhibiting hypothalamic inflammation.24
Currently, no studies have analysed whether the perioperative application of TaVNS can effectively alleviate postoperative anxiety in patients. Although TaVNS could effectively mitigate anxiety-like behaviours in mice with post-traumatic stress disorder,25 whether its perioperative use could efficiently alleviate postoperative anxiety in patients remains unexplored. This study aims to observe and evaluate the effect of TaVNS on perioperative anxiety in patients undergoing laparoscopic CRC surgery and explore its potential in reducing postoperative complications.

Material and methods

Study design
This single-centre, randomised, prospective, double-blind, controlled trial will enrol 120 patients who are scheduled to undergo laparoscopic colorectal surgery at the Cancer Hospital of Nanjing Medical University, spanning from January 2026 to May 2026. The study has received approval from the Institutional Ethical Committee of Nanjing Medical University Cancer Hospital (Approval number KY-2025-149) and will be conducted in strict compliance with the Declaration of Helsinki. Registration with the National Clinical Trial Registry System has been completed, and the registration number is ChiCTR2500112808. Currently, in the recruitment phase, patients will be rigorously screened against the inclusion criteria, and all participants will sign written informed consent forms. Following randomisation principles, the 120 patients will be assigned to either the intervention group (TaVNS group) or the control group. This report adheres to the guidelines of the Standard Protocol Items: Recommendations for Interventional Trials 2025 (SPIRIT2025) checklist of items (online supplemental additional file 1). Table 1 outlines the planned workflow for registration, intervention and measurement, and figure 1 presents the study design flowchart.

Eligibility criteria
The investigator will recognise consecutive appropriate participants for the research based on the following inclusion and exclusion criteria. Once a patient meets the eligibility criteria, the researchers will provide all participants with a comprehensive explanation of the study plan and inquire whether the patient wishes to participate in the study.

Inclusion criteria
18 years ≤ age ≤80 years.

American Society of Anesthesiologists (ASA) physical status of I–III.

Undergoing laparoscopic radical resection for CRC.

Clear understanding and voluntary participation in the study, with signed informed consent.

Ability to comprehend the study procedures and use of pain scales.

Exclusion criteria
Minimum Mental State Examination (MMSE) score ≤15.

A history of neurological or psychiatric disorders.

Substance or alcohol abuse.

Visual or hearing impairment.

Communication difficulties.

Severe cardiovascular diseases: NYHA class III or IV heart failure, acute myocardial infarction or unstable angina within the past 6 months and symptomatic severe arrhythmia or valvular heart disease.

Severe hepatic disease: cirrhosis with Child–Pugh class B or C.

Severe renal disease: chronic kidney disease stage 4 or 5 (estimated glomerular filtration rate <30 mL/min/1.73 m²) or on maintenance dialysis.

Other reasons deemed inappropriate for trial participation by the investigator.

Withdrawal criteria
The patient will be admitted to the intensive care unit after surgery.

The following are reasons for withdrawal: voluntary exit, poor adherence to the study protocol, violations of the established procedures, utilisation of alternative medications or methods that could influence the outcome measures or failure to complete the follow-up process.

Randomisation and blinding
This randomised controlled trial will utilise a 1:1 allocation ratio to distribute participants evenly into either the TaVNS group or the control group. Prior to the study commencement, a computer-generated randomisation sequence will be meticulously prepared for 120 eligible participants. Utilising this sequence, sequentially numbered, opaque and sealed envelopes containing the group assignments will be crafted. The randomisation envelope will be securely stored and managed by authorised personnel who remained uninvolved in participant recruitment, intervention administration or outcome evaluation to maintain the integrity of the blinding process. On successful enrolment of a participant, the investigator or designated staff member will contact the envelope custodian to ascertain the group assignment. The custodian, adhering to the sequential order, will then retrieve the corresponding envelope, meticulously record the participants’ screening number and initial in the designated area and sign and date the envelope on opening, thereby finalising a single randomisation procedure. Throughout the study, only outcome assessors and data analysts will be blinded to the group assignments. Patients will be randomly allocated to their respective groups, ensuring the robustness and validity of the findings.

Unblinding
During the trial, instances of unblinding may be deemed permissible under exceptional circumstances, specifically when a participant encounters severe complications or requires emergency resuscitation, and where knowledge of the assigned intervention is considered critical for effective clinical management. In addition, any unblinding will be fully documented, noting the reason, people involved and date. The integrity of the blinding protocol must be rigorously upheld for all other participants and study personnel, ensuring the continued validity and reliability of the trial outcomes.

Anaesthesia and perioperative management
On the day before surgery, the operating room nurse who will not be involved in the study will open the randomisation envelope. For eligible patients scheduled to undergo laparoscopic CRC surgery, the anaesthesiologist will conduct a final screening, record baseline assessments, complete the pre-anaesthesia evaluation, obtain informed consent (online supplemental additional file 2) and initiate the assigned intervention as per the envelope assignment.
After the patient is admitted to the operating room, peripheral venous access will be established. Standard monitoring will encompass electrocardiography, pulse oximetry, heart rate, invasive mean arterial pressure (MAP) and respiratory rate. General anaesthesia will be induced with intravenous administration of propofol (1.5–2.5 mg/kg), midazolam (0.05–0.1 mg/kg), sufentanil (0.3–0.5 μg/kg), rocuronium (0.6 mg/kg) and oxycodone (0.1–0.3 mg/kg). Anaesthesia will be maintained with continuous infusions of propofol (4–8 mg/kg/h), remifentanil (0.1–0.3 μg/kg/min), rocuronium (0.3–0.6 mg/kg/h) and dexmedetomidine (0.2–0.7 μg/kg/h). The MAP will be kept within ±20% of the baseline values. Dopamine (1 mg) or atropine (0.5 mg) will be administered if required to maintain haemodynamic stability. During the surgery, the doses of propofol and remifentanil will be titrated to maintain a bispectral index value between 40 and 60. Mechanical ventilation will be adjusted to set the tidal volume at 6–8 mL/kg, end-tidal carbon dioxide between 35 and 45 mmHg, respiratory rate of 12 breaths/min, inspiratory-to-expiratory ratio of 1:1.5-2 and oxygen flow of 1.5 L/min. 30 min prior to the end of surgery, ondansetron (8 mg) will be administered intravenously to prevent postoperative nausea and vomiting. Fluid management strategies will be tailored based on the patient’s clinical condition. All patients will receive patient-controlled analgesia with a solution of oxycodone (10 mg), sufentanil (50 µg) and ondansetron (8 mg) diluted in 0.9% saline to a total volume of 100 mL.

Study interventions
On the day before surgery, the anaesthesiologist will configure the TaVNS device (Changzhou RISHENA Medical Devices Co., Ltd., China, Medical Device Registration No. 20212090050) in accordance with the predetermined protocol (online supplemental additional file 3). Electrodes will be placed in the patient’s auricular concha region. The stimulation intensity will be individually titrated to a level that is clearly perceptible to the patient but below the threshold of significant discomfort. Specifically, this is achieved by reducing the intensity by one unit just before discomfort will become noticeable. The active stimulation group will receive 30 min of TaVNS via the concha-mounted stimulator. The sham group will wear an identical device in the same position and experience a brief, low-intensity electrical current that produces a slight tingling sensation, after which the device automatically will be turned off (figure 2). Following extubation and once the patient is clinically stable in the post-anaesthesia care unit (PACU), the aforementioned stimulation protocol will be repeated. On completion of the stimulation, the patient experiences no significant discomfort and is then transferred out of the PACU. Two time points will be selected to address the two distinct peaks of perioperative anxiety. Administering TaVNS 1 day prior to surgery is beneficial in mitigating patient anxiety stemming from anticipating the operation. This intervention also contributes to regulating the equilibrium of the autonomic nervous system and bolstering patient preparedness for the upcoming surgery. Immediately after extubation in the PACU, TaVNS is applied to ease acute anxiety triggered by pain and discomfort on awakening from anaesthesia, thereby reducing early postoperative distress and promoting recovery. This strategy combines proactive prevention with responsive intervention.

Outcomes

Primary outcome
The primary outcome is the incidence of anxiety within 3 days and 3 months after surgery. Anxiety and depressive symptoms will be assessed using the Hospital Anxiety and Depression Scale-Anxiety subscale (HADS-A, range = 0-21, with higher scores indicating greater anxiety). Data will be collected at the following time points: T0, day 1 before surgery, pre-intervention; T1, day 1 before surgery, post-intervention; T2, day of surgery, pre-intervention; T3, 2 h after surgery; T4, postoperative day 1; T5, postoperative day 2; T6, postoperative day 3; T7, 3 months after surgery. Our research assistants will collect HADS-A scores at the 3- month follow-up through structured telephone interviews.

Secondary outcome
Postoperative pain intensity will be assessed using the Numerical Rating Scale (NRS), with evaluations conducted during both rest and activity. The measurement time points are set 2 h after surgery, as well as in the morning and afternoon on postoperative days 1–3. Delirium is screened using either the 3 min Diagnostic Interview for Confusion Assessment Method (3D-CAM), as clinically appropriate. Both assessments will be performed two times daily during the first three postoperative days, with a minimum interval of 6 h between evaluations according to the following schedule: T1, morning of postoperative day 1; T2, afternoon of postoperative day 1; T3, morning of postoperative day 2; T4, afternoon of postoperative day 2; T5, morning of postoperative day 3; T6, afternoon of postoperative day 3. If delirium is detected at any assessment, daily evaluations will continue until the patient’s symptoms resolve. Sleep quality is evaluated using the Richards–Campbell Sleep Questionnaire (RCSQ). The measurement time points are the mornings of postoperative days 1–3.
The objective of this study is to investigate the impact of TaVNS on perioperative anxiety in patients undergoing laparoscopic CRC surgery. The primary outcome is measured using the HADS-A, which consists of seven items. Mild anxiety is defined as a discomfort level ranging from 8 to 10, moderate anxiety from 11 to 14 and severe anxiety from 15 to 21.

Safety evaluation
An adverse event (AE) refers to any unfavourable medical occurrence that takes place during the study period and may be related to the intervention. Investigators are required to document AEs within 24 h of their identification, and serious AEs must be immediately reported to the ethics committee and the sponsor. Meanwhile, detailed records of the AE’s name, time of onset, severity, duration, etc., should be made using paper forms. For AEs that have not resolved, continuous follow-up should be conducted until recovery or stabilisation. Safety update reports or study progress reports should be submitted regularly. TaVNS demonstrates good tolerability and adherence, with most patients experiencing no significant AEs after completing the intervention. Common adverse reactions associated with TaVNS include transient dizziness, headache, local skin irritation and itching, which generally do not require intervention and will improve spontaneously within a short period.

Data collection and management
Data collection will be systematically conducted throughout the preoperative, intraoperative and postoperative stages, employing standardised instruments and documented on case report forms (CRFs) (online supplemental additional file 4). Researchers will conduct preoperative anaesthesia evaluations and obtain informed consent from patients 1 day prior to the surgery. Preoperative assessment will include demographic characteristics, clinical baseline (height, weight, body mass index and ASA classification), surgical plan (resection location and tumour stage), frailty scale score and preoperative anxiety evaluation. Intraoperative data will be recorded by an investigator responsible for anaesthesia blinding to the group assignments in the operating room. Intraoperative monitoring will encompass vital signs, medication records and procedural durations. Postoperative outcomes will be systematically assessed using validated scales: HADS-A for anxiety, NRS for pain, 3D-CAM for delirium and RCSQ for sleep quality. The personnel responsible for postoperative follow-up and data analysis remain blinded to both the intervention and anaesthesia procedures and patient group allocations.
All data will be recorded in paper-based CRFs before manual entry into the study database. Following verification and locking, CRFs will be archived numerically with a retrieval index. Statistical analysis will be conducted by independent statisticians blinded to group allocation.

Sample size calculation
The sample size estimation for this study was performed using PASS 15.0 (Power Analysis and Sample Size Software), a validated tool extensively utilised in statistical research for determining optimal cohort sizes. Preliminary data have indicated that the incidence of perioperative anxiety in patients with CRC is approximately 40%. To the best of our knowledge, no previous studies have investigated the efficacy of TaVNS in managing perioperative anxiety in this population. In our preliminary experiment, we collected anxiety scores from 32 patients over the first three postoperative days. Among them, seven patients in the control group had HADS scores≥8, whereas three patients in the experimental group had scores≥8. According to the preliminary experimental results, the incidence of perioperative anxiety in patients with colorectal tumour in the control group was approximately 43%, whereas it was around 18% in the experimental group. This portion of results from the preliminary experiment is not included in the formal trial. Based on existing literature and clinical pre-experiment results, we anticipate that TaVNS will reduce the incidence of postoperative anxiety from 40% in the control group to 15% in the intervention group. Based on a two-tailed test (α=0.05, power=0.80), the initial sample size required to detect the anticipated effect is 94 participants. To account for an estimated 20% attrition rate, 120 patients are ultimately selected to join the study. (60 per group).

Statistical analysis
All statistical analyses will be performed using SPSS version 29.0 (IBM Corp., Armonk, NY, USA), with a two-tailed α level of 0.05 set as the threshold for statistical significance throughout the study. Continuous variables will be evaluated for normality using the Shapiro–Wilk test. Normally distributed data are reported as mean±SD and compared between groups using the independent samples t-test. Non-normally distributed data are presented as median with IQR and will be analysed using the Mann–Whitney U test. Categorical variables are expressed as frequencies (n) and percentages (%), with group comparisons conducted via the χ2 test or Fisher’s exact test, as appropriate.
The primary outcome is the incidence of perioperative anxiety in patients who receive two sessions of active or sham TaVNS intervention during the period from 1 day before surgery to 3 days after surgery. If the HADS-A score exceeds 7 points, the patient will be diagnosed with postoperative anxiety. Initially, we plan to use a scoring approach to determine the number of cases of postoperative anxiety, employing the χ2 test as the statistical method for this analysis. Additionally, for the specific scores of each patient, we will utilise multiple comparison methods to statistically analyse the differences in scores between the two groups of patients. We will employ a linear mixed-effects model to compare the occurrence of anxiety, with baseline (T0) values serving as covariates, treatment, time and the interaction between treatment and time as fixed effects and random intercepts for patients as random effects to account for temporal variations. The interaction term between treatment and time will be examined first if significant differences between treatments and across treatment groups at each time point, as well as temporal differences within treatment groups, are tested. Multiple comparison adjustments for anxiety score baseline (T0) differences within treatment groups at each time point will be conducted using the Bonferroni test. Otherwise, the main effect of treatment is tested first, and no Bonferroni correction will be applied to the treatment effects at each time point for evaluating treatment efficacy. Secondary outcomes (delirium incidence, pain scores and sleep scores) will be analysed using appropriate parametric or non-parametric tests based on data distribution. Within-group comparisons employ paired t-tests or Wilcoxon signed-rank tests; between-group comparisons use t-tests or Mann–Whitney U tests. Repeated-measures data will be analysed using a mixed linear model. In cases where there is an imbalance between groups, we will use Cox regression analysis to identify risk factors for time-to-event data. Categorical data will be analysed with χ2 or Fisher’s exact tests and ordinal data with rank-sum tests. To explore potential differences in the effects of TaVNS among different patient subgroups, we will have pre-specified the following exploratory analyses. The preliminary analysis will utilise the clinical cut-off value of the anxiety subscale from the HADS-A to categorise patients into an anxiety group and a non-anxiety group based on their preoperative anxiety levels. Additionally, we will conduct exploratory analyses to examine the effect modification roles of age and sex. All analyses will be performed by testing the interaction between the treatment group and subgroup variable in the statistical models, and the p-values for these interactions will be reported. For the main intention-to-treat analysis, all patients will be included based on their initial random assignment, even if their laparoscopic surgery is switched to open surgery. Additionally, as a sensitivity check, we will conduct a per-protocol analysis excluding patients whose surgeries are converted and only including those who completed the surgery as originally planned. Statistical significance will be set at p<0.05.

Discussion
Perioperative anxiety, a common and clinically significant issue stemming from multiple factors, substantially affects patients’ physiological and psychological recovery. Research indicates that up to 60% to 80% of adult patients experience significant levels of anxiety before surgery.46 Despite substantial advancements in surgical techniques and anaesthesia safety, anxiety remains a widespread emotional response to this major event of undergoing surgery. Of note, the incidence of perioperative anxiety among patients with colorectal tumours is significantly higher than that in patients undergoing other types of surgeries.26 Patients not only worry about their survival time due to their tumour history, but they also have an intense fear of the possible changes in bowel habits resulting from surgery and the dreadful prospect of having a stoma. Meanwhile, the application of CO₂ pneumoperitoneum during laparoscopic procedures has been demonstrated to exacerbate postoperative symptoms, including nausea and vomiting, as well as discomfort and pain localised in the shoulders and back. These adverse symptoms, in turn, contribute to a further elevation in the incidence of postoperative anxiety among patients.27 The incidence of anxiety among patients with colorectal tumours can reach as high as 52% on postoperative day 1.28 Anxiety activates the sympathetic nervous system, leading to an increased heart rate and elevated blood pressure. This renders patients more susceptible to significant cardiovascular fluctuations during the anaesthesia induction period, particularly when undergoing tracheal intubation, consequently elevating the risk of myocardial ischaemia.29 Due to the pain and low mood, patients are reluctant to get out of bed and engage in early ambulation, thereby increasing the risks of pulmonary infection, deep vein thrombosis of the lower extremities and intestinal adhesion. Therefore, the susceptibility to severe complications induced by anxiety can hinder patients’ postoperative recovery and reduce their satisfaction levels.30 Currently, perioperative anxiety management interventions have failed to deliver satisfactory outcomes, resulting in inadequate alleviation of patient anxiety, prolonged hospital stays and a substantial personal and societal burden.
Currently, the pharmacological interventions that are employed to mitigate anxiety, with benzodiazepines serving as a prime illustration, are linked to potential risks, including respiratory depression, delayed postoperative emergence from anaesthesia and a spectrum of other adverse effects. These side effects have the potential to disrupt the implementation of enhanced recovery after surgery protocols.31 Conversely, non-pharmacological strategies like psychological counselling, despite their proven benefits, frequently necessitate the involvement of specialised professionals. Moreover, such approaches may not be easily accessible across all surgical environments. Therefore, research on more effective strategies is necessary to reduce the incidence of perioperative anxiety while minimising side effects.
The VN, the longest and most intricate among the cranial nerves, extends from the brainstem down through the neck, chest and abdomen, innervating a diverse array of organs and structures. Implantable VNS is a well-established neuromodulation technique that involves implanting electrodes into the left VN trunk in the neck.32 These electrodes then transmit electrical signals to the brain, stimulating the VN and thereby influencing the brain microenvironment. VNS is widely applied in the treatment of refractory epilepsy and depression and has shown tremendous potential in the field of post-stroke rehabilitation. However, this implantable VNS could also lead to numerous complications, such as infections, bleeding, vocal cord paralysis, as well as throat pain and discomfort.33
At present, TaVNS has gained widespread application in clinical disease research owing to its non-invasive, secure and straightforward characteristics. The auricular branch of the VN, which primarily innervates the external auditory meatus and concha region, can be stimulated via TaVNS using skin-surface electrodes, with signals transmitted to the brain through the nucleus of the solitary tract and then relayed to organs for the treatment of certain clinical conditions. The anatomical foundation of TaVNS is grounded in the well-documented VN projections that extend from the auricular concha to critical brain regions implicated in emotional regulation, such as the amygdala, anterior cingulate cortex and insula.34 35 By augmenting parasympathetic activity via vagal afferent pathways, TaVNS has the potential to directly counterbalance the surgery-elicited surge in sympathetic nervous system activity. This surge represents a principal factor underlying acute anxiety and physiological stress. Animal studies also have demonstrated that TaVNS is capable of upregulating the expression of α7 nicotinic acetylcholine receptors in the hypothalamus and concurrently inhibiting the nuclear factor-κB signalling pathway, which effectively suppresses central inflammation and contributes to the alleviation of depressive and anxious behaviours.36 TaVNS could also regulate depressive mood and alleviate perioperative anxiety in patients by promoting the release of norepinephrine in the locus coeruleus and the basal lateral nucleus of the nucleus basalis, as well as 5-HT in the dorsal raphe nucleus.37 38 In addition to the direct neural modulation mechanisms previously outlined, TaVNS may also indirectly alleviate anxiety by diminishing postoperative pain. Given that acute pain serves as a significant catalyst for anxiety, TaVNS could activate descending pain inhibitory pathways and attenuate central sensitisation, ultimately reducing the incidence of postoperative anxiety.
However, currently, clinical evidence regarding the use of TaVNS for the treatment of anxiety in perioperative patients, especially for those with colorectal tumours, is lacking. The purpose of this study is to investigate whether TaVNS, a novel non-invasive neuromodulation approach, is a therapeutic option for patients experiencing perioperative anxiety. This study introduces an innovative strategy for perioperative anxiety control in patients undergoing laparoscopic radical resection for CRC, providing a novel approach for implementing multimodal management of perioperative anxiety.
This randomised controlled trial should also take into account various potential limitations. First, as a single-centre trial, our findings specifically pertain to the effect of TaVNS on perioperative anxiety in patients undergoing laparoscopic colorectal tumour surgery, and our research results need to be validated in diverse clinical settings to establish their generalisability. In the future, we will further conduct multi-centre studies and expand the sample size to validate our conclusions. Second, when calculating the sample size, we anticipated that the use of TaVNS would reduce the incidence of perioperative anxiety to 15%. However, whether the data ultimately obtained from the experiment can meet this criterion requires using PASS version 15.0 to test the incidence rate of the results and calculate the study’s power to assess the trial’s efficacy criteria. Third, although our stimulation parameters adhere to established safety guidelines, the determination of optimal dosing strategies for anxiety alleviation has yet to be accomplished. The 30-min preoperative stimulation session may constitute merely one viable intervention timing. Future research endeavours should encompass the exploration of multiple or extended stimulation protocols. Lastly, although the utilisation of self-report measures is a normative practice in anxiety research, future investigations may incorporate objective physiological biomarkers of stress response as a supplementary means. We intend to integrate supplementary haematological biomarkers indicative of anxiety, including C-reactive protein and glycosylated acute-phase protein, to enhance the validity and reliability of our findings.
Despite these limitations, the randomised controlled design employed in this study, coupled with an appropriately determined sample size and rigorous blinding procedures, substantially enhances the validity and reliability of our research findings, thereby lending strong support to the robustness of this study. TaVNS demonstrates a remarkable capability in offering a safe and non-pharmacological approach for managing perioperative anxiety, which is highly consistent with the fundamental principles of ERAS protocols. By focusing on the psychological factors in surgical recovery, TaVNS has the potential to contribute to a more comprehensive perioperative care approach. In summary, this study investigates whether TaVNS could reduce the incidence of perioperative anxiety and postoperative complications in patients, as well as elucidate the possible mechanisms. We aim to discover a novel approach to prevent the onset of perioperative anxiety, thereby facilitating patients’ perioperative recovery.

Supplementary material
10.1136/bmjopen-2025-114240online supplemental file 110.1136/bmjopen-2025-114240online supplemental file 210.1136/bmjopen-2025-114240online supplemental file 310.1136/bmjopen-2025-114240online supplemental file 4